An international observational study validating gene-expression sepsis immune subgroups.

Summary

Across 17 ICUs and 357 adults with sepsis, a rapid multiplex RNA panel (FilmArray prototype) assigned patients to high vs low risk groups, with high-risk classification consistently associated with higher 90-day mortality, especially at day 6–8. Serial endotyping decreased the proportion of high-risk patients over time.

Key Findings

• In 357 ICU sepsis patients, high-risk assignment by model 1 was associated with higher 90-day mortality at all timepoints (S1, S2, S3).
• Model 2 showed a significant mortality difference at day 6–8 (S2: 34% vs 14%, p=0.002).
• The proportion of high-risk patients declined over time, indicating dynamic immune trajectories captured by the panel.

Clinical Implications

Supports integrating rapid gene-expression panels for prognostic stratification to select patients for targeted interventions or trials and to inform intensity of monitoring.

Limitations

• Observational design without interventional testing of stratified care
• Generalizability beyond European ICUs and optimal timing of sampling require further study

Future Directions

Use the panel for prospective enrichment in adaptive trials testing immunomodulators; evaluate integration into bedside workflows and cost-effectiveness.